TNF-α Polymorphisms Research Articles

Association of TNFα and IL10 polymorphisms with pulmonary tuberculosis susceptibility in an admixed population from a high-burden region in Northeast Brazil

Association of TNFα and IL10 polymorphisms with pulmonary tuberculosis susceptibility in an admixed population from a high-burden region in Northeast Brazil

Quantitative assessment of the association between TNF-α gene polymorphisms and angina risk.

Previous investigations into the correlation between tumor necrosis factor-α (TNF-α) gene polymorphism and susceptibility to angina have produced a range of results. This study aims to clarify the potential significance of TNF-α polymorphism as a contributing factor to the onset of angina. A comprehensive review of all corresponding literature was conducted across several major databases, covering their records from inception through to March 2024. Data were synthesized using meta-analysis techniques. Notable associations were identified in various genetic comparisons: allele contrast (A vs. G: OR=0.77, 95% CI=0.70-0.86, P<0.001), homozygote comparison (AA vs. GG: OR=3.35, 95% CI=2.51-4.48, P<0.001), heterozygote comparison (GA vs. GG: OR=1.69, 95% CI=1.19-2.40, P=0.003), recessive genetic model (AA vs. GG/GA: OR=2.40, 95% CI=1.91-3.03, P<0.001), and dominant genetic model (AA/GA vs. GG: OR=1.84, 95% CI=1.27-2.65, P=0.001). Furthermore, ethnicity-based subgroup analyzes revealed that these associations were especially significant within the Asian population and unstable angina, with all genetic models demonstrating statistical significance (P<0.05). TNF-α gene is significantly associated with an increased risk of angina, particularly among the Asian population and unstable angina. This finding underscores the importance of considering genetic factors in the assessment and management of angina risk.

Influence of polymorphisms in TNF-α and IL1β on susceptibility to alcohol induced liver diseases and therapeutic potential of miR-124-3p impeding TNF-α/IL1β mediated multi-cellular signaling in liver microenvironment.

Alcoholic liver disease (ALD) is the leading cause of the liver cirrhosis related death worldwide. Excessive alcohol consumption resulting enhanced gut permeability which trigger sensitization of inflammatory cells to bacterial endotoxins and induces secretion of cytokines, chemokines leading to activation of stellate cells, neutrophil infiltration and hepatocyte injury followed by steatohepatitis, fibrosis and cirrhosis. But all chronic alcoholics are not susceptible to ALD. This study investigated the causes of differential immune responses among ALD patients and alcoholic controls (ALC) to identify genetic risk factors and assessed the therapeutic potential of a microRNA, miR-124-3p. Bio-Plex Pro™ Human Chemokine analysis/qRT-PCR array was used for identification of deregulated immune genes. Sequencing/luciferase assay/ELISA detected and confirmed the polymorphisms. THP1 co-cultured with HepG2/LX2/HUVEC and apoptosis assay/qRT-PCR/neutrophil migration assay were employed as required. The combined data analysis of the GSE143318/Bio-Plex Pro™ Human Chemokine array and qRT-PCR array revealed that six genes (TNFα/IL1β/IL8/MCP1/IL6/TGFβ) were commonly overexpressed in both serum/liver tissue of ALD-patients compared to ALC. The promoter sequence analysis of these 6 genes among ALD (n=322)/ALC (n=168) samples revealed that only two SNPs, rs361525(G/A) at -238 in TNF-α/rs1143627(C/T) at -31 in IL1β were independently associated with ALD respectively. To evaluate the functional implication of these SNPs on ALD development, the serum level of TNF-α/IL1β was verified and observed significantly higher in ALD patients with risk genotypes TNF-α-238GA/IL1β-31CT+TT than TNF-α-238GG/IL1β-31CC. The TNF-α/IL1β promoter Luciferase-reporter assays showed significantly elevated level of luciferase activities with risk genotypes -238AA/-31TT than -238GG/-31CC respectively. Furthermore, treatment of conditioned medium of TNF-α/IL1β over-expressed THP1 cells to HepG2/LX2/HUVEC cells independently showed enhanced level of ER stress and apoptosis in HepG2/increased TGFβ and collagen-I production by LX2/huge neutrophil infiltration through endothelial layer. However, restoration of miR-124-3p in THP1 attenuated such inter-cellular communications and hepatocyte damage/collagen production/neutrophil infiltration were prohibited. Target analysis/luciferase-reporter assays revealed that both TNF-α/IL1β were inhibited by miR-124-3p along with multiple genes from TLR4 signaling/apoptosis/fibrogenesis pathways including MYD88, TRAF3/TRADD, Caspase8/PDGFRA, TGFβR2/MCP1, and ICAM1 respectively. Thus, rs361525(G/A) in TNF-α and rs1143627(C/T) in IL1β gene may be used as early predictors of ALD susceptibility among East Indian population. Impeding overexpressed TNF-α/IL1β and various genes from associated immune response pathways, miR-124-3p exhibits robust therapeutic potential for ALD patients.

Polymorphism of proinflammatory inerleukin genes in primary open-angle glaucoma

Glaucoma is a degenerative disease of the optic nerve, accompanied by the death of retinal ganglion cells (RGCs) and loss of vision. An important role in the pathogenesis of glaucoma is ascribed to activated microglia, which produce pro-inflammatory interleukins and initiate GCS apoptosis. It has been established that single nucleotide polymorphisms of interleukin genes modify the development of neuroinflammation, but their effect on the risk of developing glaucoma is not yet fully established. Our aim was to determine the pathogenetic role of gene polymorphisms in TNFα and IL1β in the development of primary open-angle glaucoma.We have observed 56 patients of Russian nationality from the South of Russia with primary open-angle glaucoma (POAG), 28 patients with stage I, 16 with stage II, 12 with stage III POAG. The single nucleotide polymorphisms TNFα 308G&gt;A (rs1800629) and IL1β -31 Т&gt;С (rs1143627) were studied by restriction fragment analysis of PCR products. The level of pro-inflammatory cytokines (TNFα and IL1β) in the lacrimal fluid of patients with POAG was evaluated by enzyme-linked immunosorbent assay (Vector-Best test system). To perform optical coherence tomography by analysing the thickness of retinal nerve fiber layer (RNFL) with volume and area of the neuroretinal rim using Torson 3D OST 1000 apparatus.Results: in patients with POAG, we have found more common incidence of TNFα 308A (OR = 5.21, p = 0.001), and IL1β-31 T alleles (OR = 1.99, p = 0.04). An increased risk of developing POAG was found in carriers of genotypes 308A/A (OR = 6.30, p = 0.049), 308G/A (OR = 3.60, p = 0.049) and -31T/T (OR = 2.67, p = 0.04). The highest levels of TNFα were determined in the 308A/A group (190 (153.0-220.0) pg/mL), IL1β were in the group (-31) T/T – 6.50 (4.10-7.00) pg/mL. A decreased thickness of the retinal nerve fibers was observed in the patients with TNFα G308A genotype (59.5; 40.0 to 78.0 µm, p = 0.03), and in TNFα A308A carriers (79.0; 65.0 to 80.0 µm, p = 0.001).The TNFα 308 G/A (rs1800629), along with IL1β, -31Т/C (rs1143627) cytokine gene polymorphisms are associated with development of primary open-angle glaucoma. TNFα 308A, IL1β -31T alleles, as well as the 308G/A, 308A/A and -31T/T genotypes seem to be the risk factors for POAG in Russian population. High content of TNFα in the lacrimal fluid was found in the carriers of 308A/A genotype and -31T/T IL1β genotype. The lowest thickness of the retinal nerve fiber layer was observed in the carriers of tTNFα A308A and TNFα G308A genotypes.

Investigation of polymorphism tumor necrosis factor in multiple sclerosis: A Systematic Review and Meta-Analysis

Multiple sclerosis (MS) is an acquired disabling neurological disease of young adults, affecting approximately 2.3 million people worldwide. Multiple sclerosis is an inflammatory disease of the central nervous system (CNS), which causes a heterogeneous array of symptoms and signs because of the differential involvement of motor, sensory, visual, and autonomic systems. TNF-α is an important cytokine of the inflammatory response involved in the pathogenesis of multiple sclerosis. A systematic literature review and a meta-analysis were conducted to discuss the tumor necrosis factor-α (TNF-α) polymorphism and prognosis of MS. PubMed and Embase databases were searched to find articles published between January 2000 and December 2022. Forty eligible studies, comprising 4220 patients with MS and 5321 controls, were included in the meta-analysis. In most populations, the pooled ORs (95%CI) for TNF 2/1 versus 1/1 were 0.95 (0.82-0.99), the pooled ORs (95%CI) for TNF 2/1 versus 1/1 and TNF 2/2 versus 2/1 were not statistically significant in the overall population. In conclusion, the data from this meta-analysis study show no significant role of TNF-α polymorphism in multiple sclerosis.

Cytokine polymorphisms in patients with autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) is due to autoantibodies with or without complement activation and involves cellular and cytokine dysregulation. Here, we investigated cytokine single-nucleotide polymorphisms (SNPs) of TNF-α, TGF-β1, IL-10, IL-6, and IFN-γ, along with their serum levels. The former were related to hematological parameters, therapy, and clinical outcome. The study included 123 consecutive patients with primary AIHA [77 warm AIHA and 46 cold agglutinin disease (CAD)], followed up for a median of 49 months. Results show that the allelic frequency of TNF-α -308 G/A polymorphisms was significantly lower in patients versus controls. Moreover, the genotypic frequency of TNF-α -308G/A and TGF-β gene codon 25 G/C genotypes was significantly lower in patients versus controls. Considering cytokine SNP genotypes associated with different gene expression levels, TNF-α high gene expression was significantly more frequent in patients, TGF-β and IL-10 high gene expression was higher in patients with more severe anemia, and TGF-β high gene expression was higher in patients with active disease. Considering treatment, TNF-α and TGF-β high gene expression was more frequent in multitreated patients and particularly in CAD. It may be speculated that this genetic predisposition to a stronger inflammatory response may result in a greater immune dysregulation and in a relapsed/refractory disease. Regarding cytokine serum levels, TNF-α and TGF-β were significantly lower, and IL-10 and IL-6 were significantly higher in patients versus controls, underlying the complex interplay between genetic background and disease features.

Association between TNFα-308 G/A and IFN-γ+874A/T Polymorphisms with Oral Lichen Planus

Background: Oral lichen planus (OLP) is a chronic disease that presents with inflammation and has a global prevalence of 0.1-4%. Lesions of the disease occur in the oral mucosa, gums, and rarely in the palate. This study aimed to investigate the relationship between this disease and TNFα-308G/A and IFN-γ+874A/T polymorphisms. Methods: In this case-control study, oral mucosal samples were collected from 50 healthy subjects, and 50 OLP patients presented to the Kerman Faculty of Dentistry were enrolled using a simple sampling method. Subsequently, we used the amplification refractory mutation system polymerase chain reaction (ARMS-PCR) technique followed by sequencing to determine the presence of TNFα-308G/A and IFN-γ+874A/T polymorphisms in cases and controls. Results: Compared to the control group, the prevalence of A and GA alleles of the TNF gene was higher than the prevalence of G and GG alleles in OLP patients, while the AA genotype of the gene was not found in OLP patients. Regarding IFN gene polymorphism, the relationship between the T allele and the risk of disease was discovered, but it was not statistically significant (P value: 0.068). Conclusion: Although there is a strong relation between the A allele of TNF-α (-308G/A) polymorphism and the risk of OLP, this association between IFN-γ+874A/T genotype and the disease was not strong enough to predict the possibility of developing OLP.

A Synopsis of Hepatitis C Virus Treatments and Future Perspectives.

Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms has formed the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFNα; then, IFNα plus ribavirin (IFN-RBV); and then, pegylated-IFNα-RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients' treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV-HCV and HCV-HIV patients has also improved based on DAA and PEG-IFNα-RBV (HBV-HCV). CD4 cells are crucial for an effective antiviral response. The IFNλ3, IL28B, TNF-α, IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.

IL-6, IL-10 and TNF-α gene polymorphisms in preeclampsia: a case-control study in a Mexican population.

We focused our study on examining the genotype and allele frequency of IL-6 (rs1800795), TNF-α (rs1800629) and IL-10 (rs1800872) single nucleotide polymorphisms (SNP) on preeclampsia (PE) diagnosed Mexican pregnant women. A case-control study was designed including 86 preeclampsia patients and 100 normotensives pregnancies from Women's Hospital of Culiacan, Mexico. Genotyping of IL-6, TNF-α and IL-10 was performed using TaqMan SNP Genotyping. Not significant association was found between development of PE and genotypic (p > 0.05) and allelic (p > 0.05) frequencies of IL-6, TNF-α and IL-10 SNPs. Genotype distributions of IL-6 (p = 0.599), TNF-α (p = 0.721) and IL-10 (p = 0.761) polymorphisms in the two groups were in agreement with Hardy-Weinberg equilibrium. According to the findings, the IL-6, TNF-α and IL-10 SNPs are not exponents of susceptibility to developing PE.

The 863C&gt;A and 1031T&gt;C Single Nucleotide Polymorphisms (SNPs) in the Tumor Necrosis Factor Alpha (TNF-α) Promoter Gene May Not Be Putative Predictors of HBV Endemicity

Background: Genetic polymorphisms within the gene loci of the promoter region of tumor necrosis factor (TNF) alpha have been associated with the pathogenesis of hepatitis B virus (HBV) infection. In Uganda, there is a wide variation in the HBV endemicity, ranging from low endemicity, through moderate endemicity, to hyper-endemicity. However, the underlying reasons for this disparity in HBV burden are not fully elucidated. Thus, we aimed to test the hypothesis that the TNF-α-863C/A and -1031T/C polymorphic sites may have an effect on the difference between the burden of HBV in our country. We screened 384 participants, from which a sample of 134 was drawn, to determine the HBV, TNF-α-863C/A, and TNF-α-863T/C genotypes. The nucleotide BLAST was used to match the unknown targeted sequence obtained from the Sanger sequence against the known deposited sequence. This process unveiled the base substitution mutation and the HBV genotypes. The odds ratio (OR) and Chi-square test of proportions were used for the analysis. All the analyses were performed using SPSS version 26.0 and MedCalc software version 20.010 at 95% CI. A p &lt; 0.05 was considered statistically significant. Results: The prevalence of both the TNF-α-863C/A and the TNF-α-1031T/C genotypes and their alleles did not differ significantly by endemicity (p &gt; 0.05). However, the prevalence of the nucleotide substitution mutations for TNF-α-863C&gt;A and TNF-α-1031T&gt;C was significantly low for all the study groups (p &lt; 0.05). Conclusion: The TNF-α gene promoter at the TNF-α-863C/A and 1031T/C positions is conserved in our population and may not affect the endemicity of HBV infection. However, future research should focus on the use of nationwide samples in order to reach concreate determinations regarding the role of the TNF-α polymorphisms in the risk/resolution of HBV infections in an African or Black population.

The Role of TNF-α, TNFRSF1A, and CD40 Gene Polymorphisms in Multiple Sclerosis in the Tomsk Region

The Role of TNF-α, TNFRSF1A, and CD40 Gene Polymorphisms in Multiple Sclerosis in the Tomsk Region

Genetic Association between Inflammatory-Related Polymorphism in STAT3, IL-1β, IL-6, TNF-α and Idiopathic Recurrent Implantation Failure.

Recurrent implantation failure (RIF) is defined as a failure to achieve pregnancy after multiple embryo transfers. Implantation is closely related to inflammatory gradients, and interleukin-1beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) play a key role in maternal and trophoblast inflammation during implantation. Signal transducer and activator of transcription 3 (STAT3) interacts with cytokines and plays a critical role in implantation through involvement in the inflammation of the embryo and placenta. Therefore, we investigated 151 RIF patients and 321 healthy controls in Korea and analyzed the association between the polymorphisms (STAT3 rs1053004, IL-1β rs16944, IL-6 rs1800796, and TNF-α rs1800629, 1800630) and RIF prevalence. In this paper, we identified that STAT3 rs1053004 (AG, adjusted odds rate [AOR] = 0.623; p = 0.027; GG, AOR = 0.513; p = 0.043; Dominant, AOR = 0.601, p = 0.011), IL-6 rs1800796 (GG, AOR = 2.472; p = 0.032; Recessive, AOR = 2.374, p = 0.037), and TNF-α rs1800629 (GA, AOR = 2.127, p = 0.010, Dominant, AOR = 2.198, p = 0.007) have a significant association with RIF prevalence. This study is the first to investigate the association of each polymorphism with RIF prevalence in Korea and to compare their effect based on their function on inflammation.

TNF-α-1031T/C gene polymorphism as a predictor of malnutrition in patients with gastric cancer.

Malnutrition is a complex clinical syndrome, the exact mechanism of which is yet not fully understood. Studies have found that malnutrition is associated with anorexia and inadequate intake, tumor depletion, leptin, tumor-induced metabolic abnormalities in the body, and catabolic factors produced by the tumor in the circulation and cytokines produced by the host immune system. Among these, single nucleotide polymorphisms (SNPs) are present in the gene encoding the pro-inflammatory cytokine TNF-α. The objective of this study was to investigate TNF-α -1,031 T/C gene polymorphism as an unfavorable predictor of malnutrition in patients with gastric cancer. The study group consisted of 220 gastric cancer patients treated at Affiliated Jinhua Hospital, Zhejiang University School of Medicine. Malnutrition was mainly assessed by the Global Consensus on Malnutrition Diagnostic Criteria (GLIM). DNA was extracted from peripheral leukocytes of whole blood samples using an animal DNA extraction kit. DNA was amplified using a 1.1× T3 Super PCR mixture and genotyped using SNP1 software. There are three major genetic polymorphisms in TNF-α. Among the 220 patients with gastric cancer, there were 7 patients with the CC genotype, 61 with the CT genotype and 152 with the TT genotype. Compared to patients with the TT genotype, patients with the C allele had an approximately 2.5-fold higher risk of developing malnutrition (p = 0.003; OR = 0.406). On the basis of multivariate analysis, patients with the CC genotype had an approximately 20.1-fold higher risk of developing malnutrition (p = 0.013; OR = 20.114), while those with the CT genotype had an almost 3.7-fold higher risk of malnutrition (p = 0.002; OR = 3.218). SNP (-1,031 T/C) of the TNF-α may be a useful marker in the assessment of the risk of nutritional deficiencies in gastric cancer patients. Patients with gastric cancer carrying the C allele should be supported by early nutritional intervention, but more research is still needed to explore confirmation.

The prognostic values of the IL-10 (G1082A) and TNF-α (G308A) polymorphisms in Egyptian patients with acute lymphoblastic leukemia: A single-center study.

Interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) genes contribute to oncogenesis. We evaluated the influence of the IL-10 (G1082A) and TNF-α (G308A) polymorphisms on the prognosis and outcomes of Egyptian patients with acute lymphoblastic leukemia (ALL). We investigated 64 children and 76 adults with ALL, between 2016 and 2019, for the IL-10 (G1082A) and TNF-α (G308A) polymorphisms using allele-specific polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. Survival analyses were performed using the Kaplan-Meier estimator and the log-rank test. In children with ALL, the A allele of TNF-α and IL-10 polymorphisms was associated with older age (P = 0.04 and 0.03), more extramedullary disease (P = 0.02 and 0.001), positive breakpoint cluster region-Abelson (BCR-ABL) rearrangement (p190; P = 0.04 and 0.001), and more relapse (P = 0.002). The IL-10 GG genotype was associated with higher overall survival in children (P = 0.026). Adults carrying the TNF-α A allele showed more extramedullary disease (P = 0.009) and relapse (P = 0.003). We also found a higher frequency of IL-10 A allele in adults with older age (P = 0.03), lower hemoglobin level (P = 0.04), positive BCR-ABL rearrangement (P = 0.001), more extramedullary disease (P = 0.001), more relapse (P = 0.002), and a longer time for the first complete remission (P = 0.003). A possible association exists between the A allele of IL-10 and TNF-α polymorphisms and poor prognosis in Egyptian patients with ALL, while the IL-10 GG genotype may be associated with better survival in children with ALL.

Association of Polymorphisms in IL-10, TGF-β1, IFN-γ, and TNF-α Genes with the Susceptibility to Chronic Obstructive Pulmonary Disease in Kerman, Iran

Background: One of the principal cigarette smokes (CS) mediated diseases is chronic obstructive pulmonary disease (COPD). Methods: In the current case-control study, the relationship between the polymorphisms of interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1 ) codon 10, TGF-β1 codon 25, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) in 213 individuals with COPD and susceptibility to the disease, with 100 healthy age and gender-matched people as a control group, was investigated using PCR-ARMS (polymerase chain reaction-amplification refractory mutation system). Moreover, the combination of the polymorphisms of TGF-β1 codon 10.25 regarding this susceptibility was studied in the same condition. Results: There was a significant difference between polymorphism of TGF-β1 codon 10 (+869 T/C), codon 25 (G+915C), and susceptibility to the disease (OR=0.50; (95 %CI=0.24-1.07, p=0.05), ORCC =5.31; (95% CI: 1.22-23.2); p=0.02), thus polymorphism of IL-10 and TGF-β1 increased the risk of susceptibility to COPD but the polymorphisms of TNF-α (G-308A) and IFN-γ (+847 T/A) did not show any association. Conclusion: All in all, it is recommended that the patients carrying the above-said genotypes should be paid proper attention, especially those who are exposed to chemicals at their workplaces, pollution, and cigarette smoke.

Association between tumor necrosis factor-alpha polymorphisms (rs361525, rs1800629, rs1799724, 1800630, and rs1799964) and risk of psoriasis in studies following Hardy-Weinberg equilibrium: A systematic review and meta-analysis

ObjectivePsoriasis is a disease with an immunogenetic background in which cytokines have important effects on its prevalence and incidence. The present meta-analysis evaluated the relationship between tumor necrosis factor-alpha (TNF-α) polymorphisms (rs361525, rs1800629, rs1799724, 1800630, and rs1799964) and psoriasis risk in studies following Hardy-Weinberg equilibrium (HWE). Materials and methodsFour databases were searched to retrieve relevant studies reporting the distributions of TNF-α polymorphisms in psoriasis cases compared to controls. The effect sizes were the 95% confidence intervals (CIs) and odds ratios (ORs). Subgroup analysis, sensitivity analyses, publication bias, trial sequential analysis (TSA), and meta-regression were performed on the initial pooled results of TNF-α polymorphisms. ResultsThirty-six articles with 71 studies were included in the meta-analysis (twenty-six: rs361525, twenty-seven: rs1800629, nine: rs1799724, four: 1800630, and five: rs1799964). The pooled ORs for −238 G/A rs361525 polymorphism were 2.33 (p < 0.00001), 2.79 (p < 0.0001), 2.35 (p < 0.00001), 2.44 (p < 0.00001), and 2.45 (p < 0.00001), as well as 1.57 (p < 0.00001), 1.98 (p = 0.01), 1.61 (p < 0.00001), 1.64 (p < 0.00001), and 1.79 (p < 0.00001) for −857 C/T rs1799724 polymorphism in allelic, homozygous, heterozygous, dominant, and recessive models, respectively. Ethnicity, psoriasis type, and sample size affected the pooled results of rs361525, rs1800629, and rs1799724 polymorphisms. Based on TSA, there were just sufficient cases for −238 G/A rs361525 polymorphism in five genetic models and −857C/T rs1799724 polymorphism in allelic, heterozygous, and dominant models. ConclusionsThe A allele and GA and GG genotypes of −238 G/A rs361525 polymorphism and T allele, TT and CT genotypes of −857C/T rs1799724 polymorphism were related to increased risks in psoriasis cases. Well-designed studies (with no deviation from HWE in controls) with more cases are recommended in the future.

Genetic Polymorphism of Cytokines IL-1β, IL-4, and TNF-α as a Factor Modifying the Influence of Adverse Childhood Experiences on the Symptoms of Schizophrenia

Genetic Polymorphism of Cytokines IL-1β, IL-4, and TNF-α as a Factor Modifying the Influence of Adverse Childhood Experiences on the Symptoms of Schizophrenia

IFNγ, TNFα polymorphisms and IFNγ serum levels are associated with the clearance of drug-resistant P. falciparum in Malian children.

Host immunity has been suggested to clear drug-resistant parasites in malaria-endemic settings. However, the immunogenetic mechanisms involved in parasite clearance are poorly understood. Characterizing the host's immunity and genes involved in controlling the parasitic infection can inform the development of blood-stage malaria vaccines. This study investigates host regulatory cytokines and immunogenomic factors associated with the clearance of Plasmodium falciparum carrying a chloroquine resistance genotype. Biological samples from participants of previous drug efficacy trials conducted in two Malian localities were retrieved. The P. falciparum chloroquine resistance transporter (Pfcrt) gene was genotyped using parasite DNA. Children carrying parasites with the mutant allele (Pfcrt-76T) were classified based on their ability to clear their parasites. The levels of the different cytokines were measured in serum. The polymorphisms of specific human genes involved in malaria susceptibility were genotyped using human DNA. The prevalence of the Pfcrt-76T was significantly higher in Kolle than in Bandiagara (81.6% vs 38.6%, p<10-6). The prevalence of children who cleared their mutant parasites was significantly higher in Bandiagara than in Kolle (82.2% vs 67.4%, p<0.05). The genotyping of host genes revealed that IFN-γ -874T and TNF-α -308A alleles were positively associated with parasite clearance. Cytokine profiling revealed that IFN-γ level was positively associated with parasite clearance (p=0.04). This study highlights the role of host's immunity and immunogenetic factors to clear resistant parasites, suggesting further characterization of these polymorphisms may help to develop novel approaches to antiparasitic treatment strategies.

The Influence of TNF-α, IL-6, TGF-β1, IFN-γ, IL-10 Polymorphisms on Predisposition to Diabetes Mellitus among Jordanian Patients.

Diabetes mellitus is a long-term disorder with high prevalence globally. It can be classified into two types: Type 1 diabetes and Type 2 diabetes mellitus. Diabetes mellitus is considered a multifactorial disorder in which genetic factors such as cytokines play a major role. Cytokines play a role in immune modulation and are associated with the development of diabetes mellitus. Single nucleotide polymorphisms in cytokines were studied extensively in different populations to determine their association with a predisposition to diabetes mellitus. The aim of this study was to estimate the frequency of single nucleotide polymorphisms in the cytokine genes TNF-α, TGF-β, IL-6, IL-10, and IFN-γ in 102 Jordanian diabetes mellitus patients in comparison to 50 controls and their association to diabetes mellitus susceptibility. Analysis was performed using the highly specific polymerase chain reaction-sequence specific primers methodology. Our findings showed that the IL-10-1082 G/G genotype (P = 0.02) and the TGF-β1 codon 25*G allele (P < 0.01) may be considered risk factors for type 2 diabetes mellitus. In addition, the IFN-γ-874*A allele (P = 0.04) seems to increase the predisposition to type 1 diabetes. Our study showed that the IL-10-1082 G/G genotype and TGF-β1 codon 25*G allele are associated with type 2 diabetes mellitus while the IFN- γ -874*A allele is associated with type 1 diabetes. Our findings may help in the early detection of diabetes mellitus, which would in turn help in undergoing the needed preventative measures to delay the onset of diabetes mellitus.

The effect of ACE2 receptor, IFN-γ, and TNF-α polymorphisms on the severity and prognosis of the disease in SARS-CoV-2 infection.

To investigate the effect of genetic variations in the angiotensin converting enzyme (ACE), interferon (IFNG) and tumor necrosis factor (TNF-α) genes on the severity of coronavirus disease (COVID-19). Between September and December 2021, 33 patients with COVID-19 were included in this prospective study. The patients were classified and compared according to disease severity: mild&moderate (n = 26) vs severe&critical (n = 7). These groups were evaluated to assess possible relationships with ACE, TNF-α and IFNG gene variations using univariate and multivariable analyses. The median age of the mild&moderate group was 45.5 (22-73), and that of the severe&critical group was 58 (49-80) years (p = 0.014). Seventeen (65.4%) of the mild&moderate patients and 3 (42.9%) of severe&critical patients were female (p = 0.393). According to results of univariate analysis, the percentage of patients with the c.418-70C>G variant of the ACE gene was significantly higher in the mild&moderate group (p = 0.027). The ACE gene polymorphisms, c.2312C>T, c.3490G>A, c.3801C>T, and c.731A>G, were each only seen in separate patients with critical disease. The following variants were observed more frequently in the mild&moderate group: c.582C>T, c.3836G>A, c.511+66A>G, c.1488-58T>C, c.3281+25C>T, c.1710-90G>C, c.2193A> G, c.3387T>C for ACE; c.115-3delT for IFNG; and c.27C>T for TNF. It can be expected that patients carrying the ACE gene c.418-70C>G variant may present with a mild clinical manifestation of COVID-19. Several genetic polymorphisms may be associated with pathophysiology, as they appear to help predict COVID-19 severity and enable early identification of the patients requiring aggressive treatment.